Isostructural replacement of zinc by cadmium in bacterial metallothionein

Abstract: The class II metallothionein SmtA from the cyanobacterium Synechococcus PCC 7942 plays a major role in providing tolerance to high levels of zinc as well as a lesser role in cadmium detoxification. We previously determined the NMR structure of Zn(4)SmtA [Blindauer et al., PNAS 2001, 98, 9593-9598] and assessed its zinc-binding dynamics. In the present report, we discuss the solution structure of cadmium-loaded SmtA and provide insight into the way in which cyanobacteria manage chemically similar toxic and essential metal ions. Comparisons of 3D structures and NMR data indicate that SmtA is able to accommodate either zinc or cadmium equally well. This work is not only relevant to understanding the biological role of bacterial metallothioneins, but also has implications for metalloprotein promiscuity and specificity.